A Phase 1 interventional study of Cyclophosphamide and Fludarabine in Head and Neck Cancer, Relapse and Recurrent, sponsored by UNC Lineberger Comprehensive Cancer Center. Recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-11-05.
Sponsored by UNC Lineberger Comprehensive Cancer Center · Phase 1, Interventional, and Treatment
The purpose of this study is to test the safety and tolerability of using a new treatment called autologous T lymphocyte chimeric antigen receptor cells against the CSPG4 antigen (iC9.CAR-CSPG4 T cells) in patients with head and neck cancer that came back after receiving standard therapy for this cancer. The iC9.CAR-CSPG4 treatment is experimental and has not been approved by the Food and Drug Administration.
How many (dose) of the iC9.CAR. CSPG4 T cells are safe to use in patients without causing too many side effects, and what is the maximum dose that could be tolerated will be investigated. The information collected from the study would help cancer patients in the future.
There are two parts to this study. In part 1, blood will be collected to prepare the iC9.CAR-CSPG4 T cells. Disease fighting T cells will be isolated and modified to prepare the iC9.CAR-CSPG4 T cells. In part 2, the iC9.CAR-CSPG4 T cells are given by infusion after completion of lymphodepletion chemotherapy.
The data from the dose escalation will be used to determine a recommended phase 2 dose (RP2D), which will be decided based on the maximum tolerated dose (MTD). Additionally, recommended phase 2 dose will be tested.
Eligible subjects will receive lymphodepletion chemotherapy standard followed by infusion of iC9-CAR.CSPG4 T cells. After treatment completion or discontinuation, subjects will be followed since involving gene transfer experiments.
2,710 studies on the registry are indexed under Head and Neck Neoplasms; 594 are open to participants now.
This study's planned enrollment of 33 is below the median of 46 across 2,032 interventional studies indexed under Head and Neck Neoplasms.
Browse Head and Neck Neoplasms studies →UNC Lineberger Comprehensive Cancer Center is the lead sponsor of 429 studies on the registry; 97 are open to participants now.
Of its 33 completed or terminated interventional studies of FDA-regulated products, 26 (79%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Unless otherwise noted, subjects must meet all of the following criteria to participate in all phases of the study:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Karnofsky performance status (KPS)
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
TIA (transient ischaemic attack)
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
blood will be collected to prepare the iC9.CAR-CSPG4 T cells. Disease-fighting T cells will be isolated and modified to prepare the iC9.CAR-CSPG4 T cells. In part 2, the iC9.CAR-CSPG4 T cells are given by infusion after completion of lymphodepletion chemotherapy.
Drug: Cyclophosphamide · Drug: Fludarabine · Biological: Cell Therapy
cyclophosphamide 300 mg/meter square IV
Also known as: Cycloblastin, Cytoxan, Endoxan, Neosar, Procytox, Revimmune
fludarabine 30 mg/meter square IV × 3 days
Also known as: Fludara, Fludarabine Phosphate
the autologous T lymphocyte chimeric antigen receptor cells against the CSPG4 antigen iC9-CAR.CSPG4 T cell infusion iC9-CAR.CSPG4 T cell infusion
Toxicity: NCI-CTCAE
Toxicity will be graded as the Number of participants with adverse events (AE)s. AEs will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Dose Limiting Toxicities (DLTs) is defined as at least possibly related to CAR.B7-H3T cell product administration.
Time frame: Up to 4 weeks
Toxicity: Cytokine Release Syndrome (CRS)
CRS will be graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) CRS Consensus Grading. Grade 1 - Mild: Fever ≥38\^ o C, No hypotension, No hypoxia, Grade 2 - Moderate: Fever ≥38\^ o C, Hypotension not requiring vasopressors, Hypoxia requiring low-flow nasal cannula (≤6 L/minute) or blow-by, Grade 3 - Severe: Fever ≥ 38\^ o C, Hypotension requiring a vasopressor with or without vasopressin, Hypoxia requiring high-flow nasal cannula (\>6 L/minute), facemask, nonrebreather mask, or Venturi mask, Grade 4 - Life-threatening: Fever ≥38\^oC, Hypotension requiring multiple vasopressors (excluding vasopressin), Hypoxia requiring positive pressure (e.g. Continuous positive airway pressure, BiPAP, intubation, mechanical ventilation), Grade 5 - Death
Time frame: Up to 4 weeks
Toxicity: Immune effector cell-associated neurotoxicity syndrome (ICANS)
Neurotoxicity will be graded according to the Immune effector cell-associated neurotoxicity syndrome (ICANS) criteria. Immune effector cell-associated neurotoxicity syndrome (ICANS) symptoms will be graded according to the criteria outlined in the protocol on a scale from 1 (mild) to 4 (critical). Cytokine release syndrome (CRS) will be graded according to criteria outlined in the protocol on a scale from 1 (mild) to grade 5 (death).
Time frame: Up to 4 weeks
Dose Limiting Toxicity
An event will be considered a Dose limiting toxicity per NCI CTCAE version 5.0, the CRS Grading and ICANS grading criteria. * Grade 3-5 allergic reactions related to the CAR-T cell infusion. * A treatment-emergent Grade 3 CRS that does not improve to Grade 0-1 by 72 hours or Grade 4 CRS * Grade ≥3 ICANS that is unresponsive to the standard of care interventions and does not decrease to Grade ≤1 within 7 days or grade 4 ICANS of any duration that has evidence of cerebral edema and/or generalized convulsive status epilepticus. * Any treatment-emergent Grade 4 non-hematologic AE that does not resolve to Grade 2 within 7 days. * Any Grade 5 events are not due to the underlying malignancy.
Time frame: Up to 4 weeks
Tumor inflammation-associated neurotoxicity (TIAN)
TIAN will be assessed as a clinical endpoint using the Tumor Inflammation-Associated Neurotoxicity (TIAN) grading system, a standardized clinician-reported tool for evaluating the severity of neurotoxicity associated with tumor-related inflammatory responses, particularly following immunotherapy. Assessments will be based on neurological examination, mental status, cognitive function, focal neurological deficits, seizure activity, level of consciousness, functional status, and relevant diagnostic investigations (e.g., neuroimaging and cerebrospinal fluid analysis), as clinically indicated. Neurotoxicity will be graded on a four-level scale (Grades 1-4): Grade 1, mild symptoms; Grade 2, moderate symptoms requiring medical intervention or causing functional limitation; Grade 3, severe neurological impairment requiring hospitalization or significantly limiting self-care; and Grade 4, life-threatening neurotoxicity requiring urgent intensive management.
Time frame: Up to 4 weeks
The recommended phase 2 dose (RP2D) of iC9-CAR.CSPG4
The recommended phase 2 dose (RP2D) for administration of iC9-CAR.CSPG4 T cells will be determined based on the modified 3+3 dose finding rule and the tolerability of iC9-CAR.CSPG4 T cells. tolerability of iC9-CAR.CSPG4 T cells will be assessed by NCI-CTCAE v5, ASTCT Consensus ICANS Grading, and CRS Grading Criteria.
Time frame: Up to 4 weeks
Objective response rate
The objective response rate will be assessed per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1) and immune-related Response Evaluation Criteria in Solid Tumors (irRECIST). RECIST v1.1: Complete Response (CR) as Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; and Overall Response Rate (ORR) = CR + PR/total number of subjects. irRECIST: Complete Response (irCR), Disappearance of all lesions, no new lesions, lymph nodes \< 10 mm in short axis; Partial Response (irPR), ≥30% decrease in the sum of target lesions and non-target lesions are irNN; Stable response (irSD), not meeting criteria for irCR, irPR, or irPD; Progressive Disease (irPD), ≥20% increase in tumor burden and minimum 5 mm absolute increase in compared to nadir.
Time frame: Up to 2 years
Progression Free Survival (PFS)
PFS will be measured from the first day of lymphodepletion chemotherapy prior to iC9- CAR.CSPG4 T cell infusion to progression per RECIST 1.1 or death.
Time frame: Up to 2 years
Overall Survival (OS)
OS will be measured from the first day of lymphodepleting chemotherapy prior to iC9-CAR.CSPG4 T cell infusion to date of death for any cause.
Time frame: Up to 2 years
Duration of Response (DOR)
DOR is defined as the time from partial response (PR) or better to progressive disease (PD) per RECIST 1.1. and irRECIST.
Time frame: Up to 2 years
Feasibility of iC9-CAR.CSPG4 T cell therapy
Feasibility will be determined by measuring the percent of subjects procured that proceed with lymphodepletion followed by iC9-CAR.CSPG4 T cell infusion.
Time frame: From cell procurement to 4 weeks after iC9-CAR.CSPG4 T cell infusion.
Started Apr 2024 (actual). Primary completion is estimated for Dec 2028, 56 months after the start.
Of 89 non-industry phase 1 interventional studies under Head and Neck Neoplasms, half reached primary completion within 42 months of starting (the median), counting those still running; a quarter within 32 and three quarters within 63. This study's planned 56 months is above that.
Counting every sponsor, half of 175 studies reached it within 45 months; a quarter within 31 and three quarters within 65.
Since we started tracking on Sep 25, 2026, the dates moved once, on Nov 5, 2026: primary completion Oct 2026 → Dec 2028 and completion Aug 2028 → Nov 2030.
Earlier changes are on the record history on ClinicalTrials.gov ↗
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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